Fluoxetine treatment affects the inflammatory response and microglial function according to the quality of the living environment

Silvia Alboni, Silvia Poggini, Stefano Garofalo, Giampaolo Milior, Hassan El Hajj, Cynthia Lecours, Isabelle Girard, Steven Gagnon, Samuel Boisjoly-Villeneuve, Nicoletta Brunello, David P. Wolfer, Cristina Limatola, Marie Ève Tremblay, Laura Maggi, Igor Branchi

Research output: Contribution to journalArticle

25 Citations (Scopus)

Abstract

It has been hypothesized that selective serotonin reuptake inhibitors (SSRIs), the most common treatment for major depression, affect mood through changes in immune function. However, the effects of SSRIs on inflammatory response are contradictory since these act either as anti- or pro-inflammatory drugs. Previous experimental and clinical studies showed that the quality of the living environment moderates the outcome of antidepressant treatment. Therefore, we hypothesized that the interplay between SSRIs and the environment may, at least partially, explain the apparent incongruence regarding the effects of SSRI treatment on the inflammatory response. In order to investigate such interplay, we exposed C57BL/6 mice to chronic stress to induce a depression-like phenotype and, subsequently, to fluoxetine treatment or vehicle (21 days) while being exposed to either an enriched or a stressful condition. At the end of treatment, we measured the expression levels of several anti- and pro-inflammatory cytokines and inflammatory mediators in the whole hippocampus and in isolated microglia. We also determined microglial density, distribution, and morphology to investigate their surveillance state. Results show that the effects of fluoxetine treatment on inflammation and microglial function, as compared to vehicle, were dependent on the quality of the living environment. In particular, fluoxetine administered in the enriched condition increased the expression of pro-inflammatory markers compared to vehicle, while treatment in a stressful condition produced anti-inflammatory effects. These findings provide new insights regarding the effects of SSRIs on inflammation, which may be crucial to devise pharmacological strategies aimed at enhancing antidepressant efficacy by means of controlling environmental conditions.

Original languageEnglish
Pages (from-to)261-271
Number of pages11
JournalBrain, Behavior, and Immunity
Volume58
DOIs
Publication statusPublished - Nov 1 2016

Fingerprint

Fluoxetine
Serotonin Uptake Inhibitors
Anti-Inflammatory Agents
Antidepressive Agents
Depression
Inflammation
Prodrugs
Microglia
Inbred C57BL Mouse
Hippocampus
Pharmacology
Cytokines
Phenotype

Keywords

  • Antidepressant
  • Cytokines
  • Environment
  • Inflammation
  • Major depression
  • Microglia
  • Plasticity
  • Serotonin
  • SSRI
  • Undirected susceptibility to change hypothesis

ASJC Scopus subject areas

  • Immunology
  • Endocrine and Autonomic Systems
  • Behavioral Neuroscience

Cite this

Fluoxetine treatment affects the inflammatory response and microglial function according to the quality of the living environment. / Alboni, Silvia; Poggini, Silvia; Garofalo, Stefano; Milior, Giampaolo; El Hajj, Hassan; Lecours, Cynthia; Girard, Isabelle; Gagnon, Steven; Boisjoly-Villeneuve, Samuel; Brunello, Nicoletta; Wolfer, David P.; Limatola, Cristina; Tremblay, Marie Ève; Maggi, Laura; Branchi, Igor.

In: Brain, Behavior, and Immunity, Vol. 58, 01.11.2016, p. 261-271.

Research output: Contribution to journalArticle

Alboni, S, Poggini, S, Garofalo, S, Milior, G, El Hajj, H, Lecours, C, Girard, I, Gagnon, S, Boisjoly-Villeneuve, S, Brunello, N, Wolfer, DP, Limatola, C, Tremblay, MÈ, Maggi, L & Branchi, I 2016, 'Fluoxetine treatment affects the inflammatory response and microglial function according to the quality of the living environment', Brain, Behavior, and Immunity, vol. 58, pp. 261-271. https://doi.org/10.1016/j.bbi.2016.07.155
Alboni, Silvia ; Poggini, Silvia ; Garofalo, Stefano ; Milior, Giampaolo ; El Hajj, Hassan ; Lecours, Cynthia ; Girard, Isabelle ; Gagnon, Steven ; Boisjoly-Villeneuve, Samuel ; Brunello, Nicoletta ; Wolfer, David P. ; Limatola, Cristina ; Tremblay, Marie Ève ; Maggi, Laura ; Branchi, Igor. / Fluoxetine treatment affects the inflammatory response and microglial function according to the quality of the living environment. In: Brain, Behavior, and Immunity. 2016 ; Vol. 58. pp. 261-271.
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